Enhanced glucose tolerance in the Brattleboro rat

[Arg8]-vasopressin (AVP) plays a crucial role in regulating body fluid retention, which is mediated through the vasopressin V2 receptor in the kidney. In addition, AVP is involved in the regulation of glucose homeostasis via vasopressin V1A and vasopressin V1B receptors. Our previous studies demonstrated that vasopressin V1A receptor-deficient (V1AR−/−) and V1B receptor-deficient (V1BR−/−) mice exhibited hyperglycemia and hypoglycemia with hypoinsulinemia, respectively. These findings indicate that vasopressin V1A receptor deficiency results in decreased insulin sensitivity whereas vasopressin V1B receptor deficiency results in increased insulin sensitivity. In addition, vasopressin V1A and vasopressin V1B receptor double-deficient (V1ABR−/−) mice exhibited impaired glucose tolerance, suggesting that the effects of vasopressin V1B receptor deficiency do not influence the development of hyperglycemia promoted by vasopressin V1A receptor deficiency, and that the blockage of both receptors could lead to impaired glucose tolerance. However, the contributions of the entire AVP/vasopressin receptors system to the regulation of blood glucose have not yet been clarified. In this study, to further understand the role of AVP/vasopressin receptors signaling in blood glucose regulation, we assessed the glucose tolerance of AVP-deficient homozygous Brattleboro (di/di) rats using an oral glucose tolerance test (GTT). Plasma glucose and insulin levels were consistently lower in homozygous di/di rats than in heterozygous di/+ rats during the GTT, suggesting that the blockage of all AVP/vasopressin receptors resulting from the AVP deficiency could lead to enhanced glucose tolerance.

Research highlights
► After 16 h fasting, the plasma glucose level of AVP-deficient homozygous Brattleboro (di/di) rats was not significantly different from that of heterozygous di/+ rats.
► After 16 h fasting, the plasma insulin level of di/di rats was significantly lower than that of di/+ rats.
► The plasma glucose levels observed during the glucose tolerance test were consistently lower in di/di rats than in di/+ rats.
► The plasma insulin levels were also lower in di/di rats than in di/+ rats during the glucose tolerance test.